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Chemsex has been reported among men who have sex with men (MSM) living with HIV. There have been concerns about potentially harmful drug-drug interactions between chemsex drugs and antiretroviral therapy (ritonavir and cobicistat). We aimed to describe the prevalence and patterns of chemsex users in our HIV clinic population and to evaluate antiretroviral prescribing among chemsex users.We undertook a cross-sectional study of patients attending our HIV clinic between January 2019 and December 2020. We collected data on patients who disclosed recent recreational drug use including chemsex in the previous 3 months.In all, 2202/2501 (88%) patients were asked about recreational drug use and 514 (23%) disclosed recreational drug use. Eighty-two (4%) of these disclosed recent chemsex; 73 (89%) used crystal methamphetamine, 51 (62%) used gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL), 55 (67%) reported poly-drug use and 63 (76%) reported injecting drug use. The chemsex users were all cis-male MSM and were significantly older (53 vs. 46 years, p 0.0001), and more likely to have had previous syphilis (73% vs. 28%, p 0.0001) than patients reporting non-chemsex drug use. All chemsex users were prescribed antiretrovirals and 74 (90%) had an undetectable HIV viral load; 31 (38%) patients were taking either ritonavir (N = 12) or cobicistat (N = 19) as part of their antiretroviral regimen and this was similar to other patients attending for HIV care [31/82 (38%) vs. 768/2419 (31%), p = 0.25].The prevalence of chemsex users among our HIV clinic attendants is 4%, and 38% of these were prescribed either ritonavir or cobicistat. Chemsex use should be a factor in antiretroviral therapy decision-making to avoid potential harm.

BACKGROUND Women with HIV face challenges in engaging in HIV care post partum. We aimed to examine changes in engagement in HIV care through clinic attendance before, during, and after pregnancy, compared with matched women with HIV who had never had a recorded pregnancy. METHODS In this cohort study, we describe changes in engagement in HIV care before, during, and after pregnancy among women with HIV from the UK Collaborative HIV Cohort (CHIC) study from 25 HIV clinics in the UK with a livebirth reported to the National Surveillance of HIV in Pregnancy and Childhood between Jan 1, 2000, and Dec 31, 2017. To investigate whether changes were specific to HIV, we compared these changes to those over equivalent periods among non-pregnant women with HIV in the UK CHIC study matched for ethnicity, year of conception, age, CD4 cell count, viral suppression, and antiretroviral therapy use. Analyses were via logistic regression using generalised estimated equations with an interaction between case-control status (pregnant women vs non-pregnant women) and pregnancy or pseudo pregnancy (for non-pregnant women) stage. FINDINGS 1116 matched pairs of pregnant and non-pregnant women were included (median age 34 years [IQR 30-38], 80·1% Black African, 12·5% white). 69 330 person-months of follow-up were recorded, 25 412 in the before stage, 18 897 during, and 25 021 after pregnancy or pseudo pregnancy stages. Among pregnant women, the proportion of time engaged in care increased during pregnancy (8477 [90·5%] of 9371 person-months) and after pregnancy (10 501 [84·6%] of 12 407), compared with before pregnancy (9979 [78·5%] of 12 707). Among non-pregnant women in the control group, engagement in HIV care remained stable across the three equivalent stages (9688 [76·3%] of 12 705 person-months before pseudo pregnancy; 7463 [78·3%] of 9526 during pseudo pregnancy; and 9892 [78·4%] of 12 614 after pseudo pregnancy). The association of engagement in HIV care with pregnancy or pseudo pregnancy stage differed significantly by case-control status (pinteraction

Objectives\ud To describe the impact that the COVID-19 pandemic has had on HIV testing in Brighton and Hove, United Kingdom.\ud \ud Methods\ud All HIV tests performed in Brighton and Hove from January 2016 to June 2021 were extracted, de-duplicated and anonymized. Analysis was performed to compare the monthly numbers of tests and diagnoses before and during the pandemic across different services.\ud \ud Results\ud The number of patients having tests for HIV in sexual health services (SHS) decreased by 64% in April 2020, followed by a recovery to baseline levels by the start of 2021. Similarly, the monthly number of diagnoses decreased drastically after April 2020, with almost half of diagnoses made by SHS in 2020 occurring in the three pre-pandemic months of the year. ‘Self-sampling’, used more by women and younger patients, has contributed significantly to the recovery.\ud \ud The number of patients tested in secondary care was seemingly unaffected by the pandemic. However, testing numbers were reduced in specialist services, whereas in the emergency department (ED) testing increased four-fold (most notably in the elderly) without finding any cases.\ud \ud General practice saw decreases in both the number of HIV tests performed and the number of new diagnoses made, which had not returned to baseline by June 2021.\ud \ud Discussion\ud The COVID-19 pandemic has had a large impact on the number of HIV tests performed in Brighton and Hove with sizeable decreases in the number of patients tested likely leading to ‘missed’ diagnoses. By June 2021 testing had still not returned to normal across the city.

Background Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC). Methods/design A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA Discussion We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations. Trial registration ISRCTN 44453201, registered 19 June 2019 and EudraCT 2018–004732-30.

Gout is the most common inflammatory arthritis worldwide. Its principal risk factor is hyperuricaemia. While gout has been described in HIV patients and numerous more outdated anti-retroviral therapies (ARTs) have been implicated, there have been few recent studies. Our case–control study investigated the prevalence of and risk factors for gout in an established HIV cohort. Cases were identified from database searches using key search terms, with two age- and gender-matched controls. These were compared for demographic factors, co-morbidities, HIV factors and ART exposure. Forty-five cases with gout were identified (point prevalence 2.2%). All were male and were more likely than controls to be of black African origin. Hypertension was associated with an almost five-fold increased gout risk (OR 4.8, 95% CI 1.8–12.4). No individual drug or ART class was associated with gout in this study but exposure to non-nucleoside reverse transcriptase inhibitors had a significantly protective effect against the risk of gout (OR 0.3, 95% CI 0.1–0.9). Our data suggest that gout is common in HIV patients and that the traditional risk factors, especially hypertension, play a key role. Gout and hyperuricaemia should be regarded as a biomarker of cardiovascular disease in HIV patients as they are in the general population.

HIV is a global pandemic. However, anti-retroviral therapy (ART) has transformed the prognosis and providing compliance is good, a normal life expectancy can be anticipated. This has led to a growing population of people with chronic prevalent, treated infection living to older ages. Musculoskeletal symptoms, particularly musculoskeletal pain, is common in HIV patients and, with resumption of near-normal immune function, HIV-infected patients develop inflammatory rheumatic diseases which require assessment and management in rheumatology clinics. Moreover, it is becoming apparent that avascular necrosis and osteoporosis are common comorbidities of HIV. This review will contextualise the prevalence of musculoskeletal symptoms in HIV, informed by data from a UK-based clinic and will discuss the management of active inflammatory rheumatic diseases amongst HIV-infected patients taking ART, highlighting known drug interactions.

The Diploma in Genitourinary Medicine (DipGUM), originally called the Diploma in Venereology, has been running since 1973, hosted by the Worshipful Society of Apothecaries in Blackfriars, London. The Society of Apothecaries was founded by the Royal Charter in 1617 and is one of the few livery companies in the city of London to remain professionally based. The ancient hall has recently been refurbished; few professional exams take place in a more spectacular environment; it is almost worth taking the exam just to visit! The DipGUM is an internationally recognised qualification and is one of the exit examinations for genitourinary medicine (sexual health and HIV) higher specialist trainees in the UK. A third of candidates are specialty doctors, general practitioners and other doctors working in STI services, including integrated contraception, STI and sexual health services. To apply to take the examination, candidates are required to have at least 3 months of full-time or equivalent part-time current clinical experience in STI work and …

Objectives This was a cross-sectional study with a nested case?control analysis among a cohort of HIV-infected adults aiming to explore the prevalence of and risk factors for elective hip surgery (total hip arthroplasty and resurfacing). Methods Cases were identified from the out-patient database of HIV-infected adults attending one tertiary hospital service. For each case, five controls from the same database matched by age, gender and ethnicity were identified. From the case notes, information about demographic factors, HIV factors and risk factors for hip surgery attributable to osteoarthritis or avascular necrosis (body mass index, lipids, alcohol, comorbidities and treatment with oral glucocorticoids) was extracted. Results Among the cohort of 1900 HIV-infected out-patients, 13 cases (12 male) who had undergone hip surgery [0.7%; 95% confidence interval (CI) 0.3?1.1%] were identified, with a median age of 47 years. Eleven of the 13 cases (85%) were Caucasian and seven of the 13 were in stage 3 of HIV infection. Fewer of the cases were in the asymptomatic stage of infection compared with controls [odds ratio (OR) for stage 2 or 3 infection 4.0; 95% CI 0.8–18.5]. Ever having used oral glucocorticoids was highly significantly associated with elective hip surgery (OR 44.6; 95% CI 5.7–347.7). Conclusions Among this young cohort, the prevalence of elective hip surgery was 0.7%, with the median age at surgery being 47 years. Ever having been exposed to systemic glucocorticoids was highly significantly associated with elective hip surgery, suggesting that the principal mechanism underlying the need for surgery was avascular necrosis. There may be an increased need for elective hip surgery associated with HIV infection.

S Fidler,1 J Anderson,2 Y Azad,3 V Delpech,4 C Evans,5 M Fisher,6 B Gazzard,5 N Gill,4 L Lazarus,4 R Lowbury,7 K Orton,8 B Osoro,9 K Radcliffe,10 B Smith,11 D Churchill,6 K Rogstad12 and G Cairns13 1Imperial College London, London, UK, 2Homerton University Hospital, London, UK, 3National AIDS Trust, London, UK, 4Health Protection Agency, London, UK, 5Chelsea and Westminster Hospital, London, UK, 6Royal Sussex County Hospital, Brighton, UK, 7Medical Foundation for HIV & Sexual Health (MEDFASH), London, UK, 8Department of Health, London, UK, 9Positively UK, London, UK, 10University Hospital Birmingham Foundation NHS Trust, Birmingham, UK, 11Terrence Higgins Trust, London, UK, 12Royal Hallamshire Hospital, Sheffield, UK and 13NAM Publications/Aidsmap.com, London, UK

Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients (n = 3410) were mostly MSM (78%) and those with subtype C (n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55–2.62, P

Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P.001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naive to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

The 2008 BHIVA Guidelines have been updated to incorporate all the new relevant information (including presentations at the 15th Conference on Retroviruses and Opportunistic Infections 2008) since the last iteration. The guidelines follow the methodology outlined below and all the peer-reviewed publications and important, potentially treatment-changing abstracts from the last 2 years have been reviewed. The translation of data into clinical practice is often difficult even with the best possible evidence (i.e. two randomized controlled trials) because of trial design, inclusion criteria and precise surrogate marker endpoints (see Appendix). The recommendations based upon expert opinion have the least good evidence but perhaps provide an important reason for writing the guidelines to produce a consensual opinion about current practice. It must, however, be appreciated that such opinion is often wrong and should not stifle research to challenge it. Similarly, although the Writing Group seeks to provide guidelines to optimize treatment, such care needs to be individualized and we have not constructed a document that we would wish to see used as a ‘standard’ for litigation.

OBJECTIVES To evaluate the prevalence, impact, and risk factors for pain among a cohort of human immunodeficiency virus (HIV)-infected adults treated with combination antiretroviral therapy if indicated according to current guidelines. METHODS This was a cross-sectional epidemiological observational study. All patients attending 1 HIV-outpatient center in the United Kingdom in a 10-month period were eligible. Patients completed a validated questionnaire enquiring about demographics, HIV factors, and symptoms of pain. RESULTS Of 1050 eligible participants, 859 (82%) completed a questionnaire. The 1-month period prevalence of pain lasting >1 day was 62.8% among whom 63% reported current pain. The prevalence of pain at most anatomic sites was broadly similar to that observed in population studies using the same questionnaires except that we found considerably higher rates of foot/ankle pain. The median duration of pain was 3 years (range, 0 to 51 y) and the median pain score was 5.0 on an 11-point visual analogue score. Over 40% of people in pain had consulted their primary care physician and >20% were taking analgesics daily. Independent risk factors for current pain were older age (P=0.001), time since diagnosis of HIV infection (P=0.001), and receipt of a protease inhibitor-based regimen (P=0.04). DISCUSSION Pain, and notably foot/ankle pain, is common among adults living with prevalent HIV and is associated with substantial morbidity and health care utilization.

A multitude of rheumatologic manifestations have been associated with HIV infection and protease inhibitors use. We describe two cases that display a temporal relationship between initiating Kaletra and developing Achilles tendinopathy. Immediate and dramatic resolution of symptoms occurred on switching from Kaletra to an alternative agent. Clinicians may want to consider a trial of an alternative agent in individuals on Kaletra who experience Achilles tendinopathy. Adverse events must be formally reported so that our understanding of antiretrovirals may continually evolve and aid decisions about antiretroviral prescribing.

This article reports on the extended follow-up of 125 antiretroviral (ARV)-naive patients treated with nevirapine (NVP) in the United Kingdom. The patients have been observed for a median of 1.8 years after starting NVP (range, 4 days-2.7 years). Baseline CD4 counts and HIV RNA levels were 210 (interquartile range, 130 - 335) cells/mm3 and 4.86 (range, 4.52-5.26) log10 copies/ml, respectively. Eleven patients (9.0%) developed a rash thought to be related to NVP, of whom 4 permanently discontinued NVP. Twenty-four months after starting NVP, RNA levels had dropped by a median of 2.32 log10 copies/ml and CD4 counts increased by a median of 143 cells/mm3. In all, 96 patients had at least one viral load measured500 copies/ml, a median of 2.8 months after starting NVP. RNA levels rebounded500 copies/ml in 37 of these patients, on average 2 years after initial response. In conclusion, in ARV-naive patients, NVP is generally well tolerated and long-term response rates are good.

HIV-1 is characterised by extensive genetic variability encompassing at least 10 different phylogenetically related clades within the major group of HIV-1 subtypes. Most commercially available HIV-1 RNA plasma viral load assays have been optimised with clade B viruses and may yield misleadingly low RNA levels for nonclade B viruses that are increasingly found in Europe. In this study we compare the most recent versions of the Roche Amplicor HIV Monitor and the Chiron Quantiplex for ability to detect viraemia in a population of patients infected with a range of HIV-1 subtypes. EDTA-treated plasma was obtained from 206 patients. The Amplicor and Quantiplex assays were carried out in accordance with manufacturers' instructions. Results from 53/206 (25.7%) samples differed by >0.4 log between Amplicor 1.5 and Quantiplex 3.0. A >0.5 log and 1.0 log difference was detected between Amplicor 1.5 and Quantiplex 3.0 in 37/206 (17.9%) and 7/206 (3.4%) of samples, respectively. Overall, Amplicor 1.5 gave a median value of 0.22 log higher than Quantiplex 3.0. Discordant results were detected in 53 out of 206 (25.7%) samples. Of these 22 out of 123 (17.9%) samples were of UK origin, 18 out of 43 (41.9%) African, 1 out of 8 (12.5%) South American, 1 out of 6 (16.7%) North American, 4 out of 9 (44.4%) North European, 3 out of 11 (23.7%) South European and 3 out of 7 (42.3%) Asian samples, respectively. Serotyping revealed that discordant viral load results between Amplicor 1.5 and Quantiplex 3.0 occurred within samples from all subtypes (A-E). Despite the improvements made to both the Roche Amplicor and the Chiron Quantiplex assays discordant results were detected between the two assays in 25.7% of cases. In a substantial minority of patients there were major discrepancies between the two assays that were not explained by HIV subtype differences.

Combination antiretroviral therapy, usually consisting of 2 nucleoside analogue reverse transcriptase inhibitors and a protease inhibitor (PI), has revolutionised the management of patients with HIV infection. PI-containing combinations are significantly superior to combinations of 2 nucleoside analogues, and the latter combination is now indicated only in very exceptional circumstances. However, long term adherence to complex regimens of antiretroviral drugs, and the emerging longer term toxicity associated with PIs and to a lesser extent, problems with long term adherence to complex regimens of antiretroviral drugs, make the use of 'protease-sparing' regimens attractive. Although in some cases such regimens may be associated with a lower chance of sustained suppression of viral load, leading to the development of drug resistance and virological rebound, they allow the preservation of a whole class of antiretrovirals for later use, avoid the risk of PI toxicity, and their use can also help to avoid important drug interactions associated with PIs.

Summary Background Lamivudine (3TC) and emtricitabine (FTC) are guideline choices for combination highly active antiretroviral therapy (HAART). 3TC has a shorter intracellular half life than FTC and may be more likely to lead to the development of drug resistant HIV variants. Methods In this study we analysed linked data from the observational UK Collaborative HIV Cohort (CHIC) Study and UK HIV Drug Resistance Database (HDRD) to investigate the rate of development of K65R or M184V resistance mutations in patients failing on combinations containing tenofovir (TDF) and efavirenz (EFV) with either 3TC or FTC. Virological failure was defined as 1 viral load >400 copies/ml. Rates were stratified by demographic variables, baseline viral load, current CD4 count, current viral load and year of starting regimen. Significant associations were identified using Poisson regression models and multivariable analyses were performed adjusting for the variables above. Logistic regression was used to determine whether there were any significant associations between type of regimen and detection of resistance mutation. Results 5455 patients received either (or both) 3TC, TDF and EFV or FTC, TDF and EFV contributing 6465 treatment episodes over 9962 person-years follow up. 47 of these episodes were preceded by resistance tests showing development of K65R or M184V mutation and were hence excluded. The majority of treatment episodes consisted of FTC- ( n = 5190) rather than 3TC- ( n = 1228) based regimens. 21 cases of K65R were detected over the course of follow up, giving an overall event rate of 0.21 (95% CI: 0.12–0.31)/100 person years follow up (PYFU). The overall event rate for detection of M184V was 0.38 (95% CI: 0.26–0.5)/100 PYFU. 201 patients receiving either regimen for the first time experienced virological failure. Of those receiving 3TC ( n = 53), 7 (13.2%), 12 (22.6%) and 15 (28.3%) developed K65R, M184V and either K65R or M184V respectively. Of those receiving FTC ( n = 148), 13 (8.8%), 20 (13.5%) and 26 (17.6%) developed K65R, M184V and either K65R or M184V respectively. Although patients on 3TC were more likely to develop resistance, this was not statistically significant in univariable (OR 1.85 (95% CI: 0.89–3.85, p = 0.09)) or multivariable analyses (OR 1.89 (95% CI: 0.89–4.01, p = 0.1)). Conclusions We have not found evidence of an increased risk of development of M184V and K65R in patients exposed to 3TC.

Background/introduction Training and continuing professional development in HIV medicine requires knowledge of the history of HIV. Locally we have instigated an HIV film club. There is no literature on the impact of HIV medical education using film. To date, we have had 2 educational events using “How to Survive a Plague” [Producer: D.France, 2013] and “We were Here”, [Producers: D. Weissman & B.Weberdate, 2011]. Methods An anonymous electronic survey was sent to 13 participants exploring what they had learnt, influence on practice and their opinion on the importance of the history for trainees. Results 10/13 completed the survey. 10/10 (100%) had learnt something new: appreciating HIV stigma in greater depth, recognition of the role of HIV negative MSM support and the importance in mechanisms for licensing new HIV drugs. 4/10 (40%) reported a change in practice such as a greater awareness of the psychological impact on long term survivors. 3/10 (30%) said that the films had underpinned and increased their understanding of the importance of Pre- exposure Prophylaxis (PrEP) and Direct Acting Antivirals provision in hepatitis C for patients currently. 10/10 (100%) felt it was important to have an comprehension of the history and stigma of HIV. Additional film recommendations included: “And the Band Played On” [Spelling, 1994], “Philadelphia” [J.Demme, 1993] and “Angels in America” [C.Costas, 2003]. Discussion/conclusion Innovation and progress in HIV medical education requires exploring new models of teaching: using the medium of film is ideal for HIV medicine where the field has transformed beyond recognition. Film nights were useful and interesting.

Objective To evaluate whether the prevalence of HIV-1 transmitted drug resistance has continued to decline in infections probably acquired within the United Kingdom. Design Multicentre observational study. Setting All UK public laboratories conducting tests for genotypic HIV resistance as a part of routine care. Participants 14584 patients infected with HIV-1 subtype B virus, who were first tested for resistance before receiving antiretroviral therapy between January 2002 and December 2009. Main outcome measure Prevalence of transmitted drug resistance, defined as one or more resistance mutations from the surveillance list recommended by the World Health Organization. Results 1654 (11.3%, 95% confidence interval 10.8% to 11.9%) patients had one or more mutations associated with transmitted HIV-1 drug resistance; prevalence was found to decline from 15.5% in 2002 to 9.6% in 2007, followed by a slight increase to 10.9% in 2009 (P=0.21). This later rise was mainly a result of increases in resistance to nucleos(t)ide reverse transcriptase inhibitors (from 5.4% in 2007 to 6.6% in 2009, P=0.24) and protease inhibitors (1.5% to 2.1%, P=0.12). Thymidine analogue mutations, including T215 revertants, remained the most frequent mutations associated with nucleos(t)ide reverse transcriptase inhibitors, despite a considerable fall in stavudine and zidovudine use between 2002 and 2009 (from 29.4% of drug regimens in 2002 to 0.8% in 2009, from 47.9% to 8.8%, respectively). Conclusions The previously observed decline in the prevalence of transmitted drug resistance in HIV-1 infections probably acquired in the UK seems to have stabilised. The continued high prevalence of thymidine analogue mutations suggests that the source of this resistance may be increasingly from patients who have not undergone antiretroviral therapy and who harbour resistant viruses. Testing of all newly diagnosed HIV-1 positive people should be continued.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

Eighteen patients with symptomatic HIV disease were enrolled into a phase I/II study of a microsphere formulation of the HIV protease inhibitor KNI-272, with doses escalated up to a maximum dose of 60 mg/kg/day. One patient developed reversible elevation in hepatic transaminase. The plasma half-life of the drug was very short, varying between 0.25 and 1.1 h. No consistent effect on plasma HIV RNA levels or CD4(+) lymphocyte counts was seen.

The best management strategy for HIV patients who fail to respond to first-line therapy for Pneumocystis jirovecii pneumonia is currently unclear. We identified all patients who were treated with trimetrexate and folinic acid who failed 7 or more days of cotrimoxazole, clindamycin-primaquine or dapsone-trimethoprim between 1996 and 2006. Trimetrexate was tolerated in 100% of cases with no treatment termination secondary to adverse drug reactions. Despite severe disease, 71% of patients were alive after 12 weeks.

Background HIV is a well-known cause of dilated cardiomyopathy, with an annual incidence of 15.9 per 1000 asymptomatic HIV patients in the pre-HAART era. Despite reduced incidence with HAART, it remains an important cause of cardiac morbidity in people with HIV though its direct association to the virus is unclear. Methods Retrospective case review. Results Four patients with dilated cardiomyopathy were identified out of 4739 attending between 2002–2014. Mean age was 49 years (range 38–62), all were male. Two presented as admissions with cardiac failure; two were diagnosed on routine investigation for exertional dyspnoea. All clinically improved with medical management; the three cases under long term follow up (6–10 years) showed improvement in ejection fraction (EF), though one died 10 years post diagnosis of presumed sudden-cardiac death. Discussion This small case series highlights the positive outcomes with medical management of dilated cardiomyopathy in HIV. The direct role of HIV remains unclear; these cases reinforce the importance of regular screening for recreational drug use and consideration of their potential cardiotoxicity, and awareness of other aetiological factors.

We report a case of primary pneumococcal peritonitis in a 28-year old previously healthy woman. There are no previously reported associations between this rare form of spontaneous peritonitis and HIV infection, and it is usually associated with underlying cirrhosis, ascites or other immune compromise. In this case this was the presenting illness of HIV infection. When atypical infections such as this arise in previously healthy adults the clinician must have a high index of suspicion of HIV or other underlying immunodeficiency.

Background Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. Methods A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy. Results Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir. Conclusions Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

Background: Little is known about the long term risk of development of HIV-1 drug resistance for patients starting antiretroviral therapy (ART) with three or four drug regimens in routine clinical practice. Methods: We analysed a large cohort study of patients seen in one of six large HIV clinics in and around London, UK. The focus of this analysis was on patients who started ART with two nucleosides plus either a single protease inhibitor (PI), a PI with ritonavir, abacavir or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Results: 4306 patients were followed; 1436 (33%) started with a single PI, 279 (6%) with a PI plus ritonavir, 156 (4%) with triple nucleosides and 2435 (57%) with an NNRTI. The overall cumulative risk of viral load failure was 38% by 6 years. Risk of > or =1 major IAS-USA mutation was 27% by 6 years; risk of mutations from at least two of the three main drug classes was 20% over the same period. These are lower limit estimates as test results were not available for many with viral load failure. Risk of PI mutations being detected in people who started ART with regimens containing a PI with ritonavir was significantly lower than the risk of NNRTI mutations being detected in those starting with NNRTI-containing regimens (relative hazard 0.3195% CI 0.15-0.61; p = 0.0008). Conclusion: In routine practice, rates of viral load failure and of resistance detection in patients who started ART with three or four drugs are appreciable.

Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.

Objectives: To examine rates of culture proved tuberculosis in HIV infected patients in three specialist centres in north central London. Methods: Cases of tuberculosis in patients with previously documented HIV infection from 1990 to 1996 were identified retrospectively from microbiological/clinical records at Chelsea and Westminster, St Mary's, and University College London Hospitals. Results: Between 1990 and 1996 202 cases of culture proved tuberculosis were identified at the three centres. Of these, 132/202 (65.3%) occurred in homosexual/bisexual men, 41/202 (20.3%) were in patients with heterosexual contact in sub-Saharan Africa, and 29/202 (14.4%) were in "others." Overall 148/202 (73.3%) had pulmonary tuberculosis. The total number of HIV infected individuals seen at the three centres increased from 4298 in 1990 to 5048 in 1996. Rates of tuberculosis in the three centres increased from 0.46% in 1990 to 0.83% in 1996. Part of this increase was due to an increase in tuberculosis among Africans from 1993 to 1996. Conclusions: Rates of HIV associated tuberculosis increased in these three centres in north central London between 1990 and 1996. In part this was due to an increase in the number of African patients with HIV infection attending the three centres. In addition, there was circumstantial evidence of recent transmission among homosexual men with HIV infection. Prospective "real time" surveillance of tuberculosis in HIV infected patients is needed in order to detect case clustering and to improve tuberculosis control. Key Words: tuberculosis; HIV; nosocomial transmission; multidrug resistant tuberculosis

Thirteen protease inhibitor-naive patients with HIV-1 infection, and 12 patients with a median of 58 months prior treatment with saquinavir (SQV) monotherapy, were treated with SQV (400 mg twice daily) and ritonavir (RIT, 500 mg twice daily) in a study designed to assess the effect of prior treatment with SQV monotherapy on the antiretroviral activity of RIT-SQV combination therapy. Median baseline viral load and CD4+ cell counts were 155,000 and 262,000 copies/ml and 333 and 225 cells/mm3 in the naive and experienced groups, respectively. Mean viral load changes at 24 weeks were -1.63 and -0.27 log copies/ml in the naive and SQV-experienced groups, respectively (intent-to-treat analysis). Baseline genotype by point mutation assay and sequencing in the SQV-experienced group was highly predictive of virological response. Eight of 11 SQV-experienced patients had evidence of phenotypic resistance to RIT at baseline, despite previous treatment with SQV only. There was strong correlation between phenotypic resistance to RIT and the presence of the L90M mutation. We conclude that prolonged prior treatment with saquinavir monotherapy may produce cross-resistance to ritonavir and reduce the subsequent response to ritonavir-saquinavir in combination. In this study, both phenotypic resistance to ritonavir and presence of the L90M mutation predicted the viral load response to ritonavir-saquinavir.

Lymphogranuloma venereum (LGV) is a sexually transmitted infection that is caused by Chlamydia trachomatis types L1, L2, and L3.1 Although endemic in some tropical countries, lymphogranuloma venereum is usually uncommon in the United Kingdom.1 The classical presentation of LGV is with genital ulceration (which may be asymptomatic or transient) and associated painful inguinal lymphadenopathy (or bubo), but it may also present with proctitis, extragenital lymphadenopathy, and systemic symptoms, including fever.1 Response to treatment of early infection is usually excellent. Untreated infection, however, can result in lymphatic obstruction and fibrosis, leading to genital elephantiasis, or, if involving the rectum, the formation of strictures and fistulas. In January 2004, genitourinary doctors in Europe were alerted to the existence of a cluster of cases of lymphogranuloma venereum presenting as a rectal syndrome in men who have sex with men with HIV infection.2 We describe three cases of LGV for which diagnosis was considerably delayed because the possibility of this infection was not considered. ### Case 1 A 33 year old HIV positive man who has sex with men presented to his general practitioner in May 2003 with a short history of perianal pain accompanied by discomfort on sitting. His HIV disease was well controlled with antiretroviral therapy, and his CD4 lymphocyte count was 799 × 109/l. His symptoms persisted and he developed rectal bleeding accompanied by the passage of mucus, with alternating diarrhoea and …

BACKGROUND\ud \ud Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count

A retrospective review of all 248 liver biopsies performed in patients with HIV infection at two referral centres in London over a 12 year period revealed five cases of major bleeding following biopsy, with four deaths. The risk of major bleeding was 2.0%, and mortality was 1.6% following liver biopsy. The risk of bleeding as much higher than in published series of biopsies done in patients without HIV infection, owing in part to the high prevalence of thrombocytopaenia and clotting abnormalities in patients with HIV infection. HIV infection per se may also increase the risk of bleeding following liver biopsy.

Gastrointestinal disease occurs in the majority of patients with the acquired immunodeficiency syndrome (AIDS). Opportunistic gut infection and neoplasia occur throughout the gut. The differential diagnosis of HIV-related gastrointestinal symptoms is large and includes tumours and a variety of opportunistic infections. Multiple pathology is common. Investigation of gastrointestinal symptoms is important as many pathogens will respond to specific therapy, although relapse is common and long-term treatment may be necessary. Where specific treatment for gastrointestinal disease is not available or has been unsuccessful it is always possible to palliate patients’ symptoms and improve their quality of life. This chapter aims to describe some of the more common gastrointestinal problems that physicians are likely to encounter and to provide guidelines for investigation and management.